ArticlebioRxiv : the preprint server for biology2026
Age-associated increases in inter-individual gene expression variability across human tissues.
Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Aging involves progressive physiological decline, yet the underlying transcriptomic patterns remain poorly understood. Although differentially expressed genes (DEGs) have been the primary focus of previous studies, here we investigate differentially variable genes (DVGs) using a novel Gene Stability Score (GSS). In 30 tissue types from nearly 1,000 individuals in the Genotype-Tissue Expression (GTEx) project, age- and sex-related DVGs account for approximately 15% of overall expression variability between samples of the same tissue, with age-related DVGs specifically contributing 7.7%. We further show that DEGs and DVGs affect distinct biological pathways, and that inter-individual instability is significantly correlated with cell-to-cell transcriptional noise. Moreover, gene regulatory network analysis reveals that this variability is not random but is shaped by local network architecture. Finally, we identify robust reference genes, including
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